The long term objective of the proposed research is to understand the genetic mechanisms by which the body segments of Drosophila become morphologically differentiated from one another during development. This process is known to be controlled in a large part by a gene cluster called the bithorax gene complex (BX-C). This gene complex contains at least eight, and probably many more, genes which are required for the normal development of all segments posterior to the second thoracic, or wingbearing, segment. The BX-C genes known are located, with one exception, in the same order on the chromosome as the order of body segments that these genes control. The portion of the BX-C controlling the development of the third thoracic and first abdominal segments has been studied for many years and is well characterized. The regions of the BX-C that are required for normal development of the posterior abdominal segments and genitalia, however, were discovered only relatively recently and are stil poorly understood. The major goal of the proposed research is to fully characterize these regions of the BX-C. Genetic and molecular methods will be employed to identify and study all BX-C genes required for posterior body segment specialization. These investigations should provide a much more detailed picture of how body segments are differentially specified than is now available and should test whether the properties so far defined for the BX-C are maintained throughout the complex. In addition to study of the BX-C genes themselves, a second goal of the proposed research is to characterize unlinked genes that appear to function as negative regulators of genes within the complex. During my postdoctoral work, five such regulatory genes were identified and experiments are planned to characterize these genes and their interactions so that the role played by each in the control of the BX-C can be determined. Since the specification of body regions in Drosophila may not be so different from this specification in humans, the health significance of the proposed research is that it may provide a better understanding of human embryonic development and, therefore, of certain types of congenital abnormality.